Sleep disordered breathing affects 2-5 percent of the adult population, and it is estimated that 25 percent of people over the age of 65 experience some sleep apnea. This proposal will explore age-related changes in a neurotransmitter system involved in sleep disordered breathing. We propose to determine whether serotonin is a potential mediator of the age-associated changes in upper airway control that negatively impact on breathing during sleep. Changes in serotonergic input may predispose aging individuals to disordered breathing syndromes including obstructive sleep apnea (OSA). Our working hypothesis is that serotonergic modulation of upper airway motoneurons decreases with increasing age. Preliminary results suggest that there is a decrease in serotonergic innervation of hypoglossal motoneurons in older animals, We propose to further elucidate changes in the serotonergic system by investigating age-associated changes in serotonin terminal density, specific serotonin receptors, and the selective serotonin transporter in brainstem nuclei that selectively innervate upper airway musculature. As obstructive sleep apnea occurs with greater frequency in males, a second goal of this project is to determine whether age-associated changes in the serotonergic input to these nuclei are dissimilar in males and females. A third goal of this project is to determine whether serotonergic input to the upper airway control system can be enhanced in old animals by a behavioral intervention. Preliminary results indicate that chronic, intermittent hypoxia produces a serotonin-dependent enhancement of respiratory activity in the hypoglossal motor nucleus of young rats, and an increase in serotonergic innervation. The information derived from these studies will increase our understanding of the potential mechanisms underlying age-associated sleep disorders, and open up an area of research that will hopefully lead to successful therapeutic intervention.